Chronic rhinosinusitis (CRS) is one of the most common chronic diseases, affecting 14-16% of the US population, resulting in annual direct costs of $4.3 billion and substantially reducing health- related quality of life (QOL) and olfactory function. Due to the chronicity of the disease, and the relatively poor response of many patients to medical treatment, patients with CRS undergo 500,000 surgical procedures annually, with the primary goal of improving QOL. While surgery has been successful for many patients, about 35% are thought to experience a poor surgical outcome. Furthermore, little is known of the medical treatment outcomes for this patient population. Prior studies attempted to relate several patient characteristics to the presence and severity of inflammation as a way to predict outcomes of treatment. While these clinical phenotypes provide some predictive information, data demonstrate heterogeneity even within these clinical phenotype subgroups with regard to severity of inflammation and outcomes of treatment. Work from others and preliminary data have identified important inflammatory markers in the sinonasal mucosa that may provide complementary predictive information to predict outcomes of treatment. However, important questions remain. In order to optimize patient selection for surgery and improve patient counseling on prognosis with medical vs surgical therapy, it is important to determine outcomes in patients treated medically. Another important question is whether mucosal inflammatory markers present at baseline can provide prognostic information that is superior to that provided by patient characteristics and standard diagnostic tests. The studies proposed are hypothesis-testing or hypothesis-generating in nature. Specific Aim 1 utilizes biostatistical methods to evaluate and reduce bias in comparing disease-specific, general QOL, and olfactory outcomes of patients electing medical treatment of CRS to those electing surgical treatment. Specific Aim 2 measures cellular, histological, and molecular markers of inflammation in the sinonasal mucosa at baseline in both medical treatment and surgical treatment cohorts and correlates them to baseline clinical measures of CRS disease-severity. Specific Aim 3 develops comprehensive models of multiple pretreatment factors including sociodemographic, clinical, radiographic, and inflammatory markers to predict disease-specific QOL outcomes of CRS management. Given that an RCT is not possible at this time, these aims will be completed by performing a prospective observational cohort study to evaluate medical vs surgical treatment outcomes of CRS utilizing methods to evaluate and adjust for bias and unmeasured confounders. In addition, novel mucosal markers of inflammation will be measured at baseline and evaluated for their usefulness in predicting treatment outcome. PUBLIC HEALTH RELEVANCE: Chronic rhinosinusitis is one of the most common chronic diseases, which affects 14-16% of the US population and substantially reduces health-related quality of life and olfactory function. It primarily affects the working population, leading to 73 million total restricted activity days per year, annual direct costs of $4.3 billion, and a significant economic burden in the US. This application examines ways to predict who will benefit from medical vs surgical treatment and evaluate the impact on quality of life.